6ZCD

VEGF-A 13:107 crystallized with 1C bicyclic peptide

6ZCD の概要

• エントリーDOI: 10.2210/pdb6zcd/pdb
• 関連するPDBエントリー: 6Z13 6Z3F 6ZBR
• 分子名称: Derived from V114 peptide, Vascular endothelial growth factor A, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• 機能のキーワード: growth factor, peptide ligand, lactam bridge, alpha-helix stabilization, signaling protein, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24881.74

構造登録者

Gaucher, J.-F.,Broussy, S.,Reille-Seroussi, M. (登録日: 2020-06-10, 公開日: 2021-06-23, 最終更新日: 2024-11-20)

主引用文献

Gaucher, J.F.,Reille-Seroussi, M.,Broussy, S.
Structural and ITC Characterization of Peptide-Protein Binding: Thermodynamic Consequences of Cyclization Constraints, a Case Study on Vascular Endothelial Growth Factor Ligands.
Chemistry, 2022

PubMed Abstract: Macrocyclization constraints are widely used in the design of protein ligands to stabilize their bioactive conformation and increase their affinities. However, the resulting changes in binding entropy can be puzzling and uncorrelated to affinity gains. Here, the thermodynamic (Isothermal Titration Calorimetry) and structural (X-ray, NMR and CD) analysis of a complete series of lactam-bridged peptide ligands of the vascular endothelial growth factor, and their unconstrained analogs are reported. It is shown that differences in thermodynamics arise mainly from the folding energy of the peptide upon binding. The systematic reduction in conformational entropy penalty due to helix pre-organization can be counterbalanced by an unfavorable vibrational entropy change if the constraints are too rigid. The gain in configurational entropy partially escapes the enthalpy/entropy compensation and leads to an improvement in affinity. The precision of the analytical ITC method makes this study a possible benchmark for constrained peptides optimization.

PubMed: 35665969
DOI: 10.1002/chem.202200465

実験手法

X-RAY DIFFRACTION (1.8 Å)